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Wnt/β-Catenin Signaling in Liver Pathobiology 肝脏病理生物学中的 Wnt/β-Catenin 信号转导
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-09-11 DOI: 10.1146/annurev-pathmechdis-111523-023535
Matthew D. Carson, Kari Nejak-Bowen
{"title":"Wnt/β-Catenin Signaling in Liver Pathobiology","authors":"Matthew D. Carson, Kari Nejak-Bowen","doi":"10.1146/annurev-pathmechdis-111523-023535","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023535","url":null,"abstract":"The liver has a critical role in regulating host metabolism, immunity, detoxification, and homeostasis. Proper liver function is essential for host health, and dysregulation of hepatic signaling pathways can lead to the onset of disease. The Wnt/β-catenin signaling pathway is an important regulator of liver homeostasis and function. Throughout life, hepatic Wnt/β-catenin signaling contributes to liver development and growth, metabolic zonation, and regeneration. Extensive research has demonstrated that aberrant Wnt/β-catenin signaling drives liver pathologies, including cancers, steatohepatitis, and cholestasis. In this review, we discuss the Wnt/β-catenin pathway as it pertains to liver function and how disruptions in this pathway contribute to the onset and progression of liver diseases. Further, we discuss ongoing research that targets the Wnt/β-catenin pathway for the treatment of liver pathologies.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"7 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Somatic Mosaicism in Brain Disorders. 脑部疾病中的体细胞嵌合。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-09-03 DOI: 10.1146/annurev-pathmechdis-111523-023528
Rachel R Corrigan, Lauren M Mashburn-Warren, Hyojung Yoon, Tracy A Bedrosian
{"title":"Somatic Mosaicism in Brain Disorders.","authors":"Rachel R Corrigan, Lauren M Mashburn-Warren, Hyojung Yoon, Tracy A Bedrosian","doi":"10.1146/annurev-pathmechdis-111523-023528","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023528","url":null,"abstract":"<p><p>Research efforts over the past decade have defined the genetic landscape of somatic variation in the brain. Neurons accumulate somatic mutations from development through aging with potentially profound functional consequences. Recent studies have revealed the contribution of somatic mosaicism to various brain disorders including focal epilepsy, neuropsychiatric disease, and neurodegeneration. One notable finding is that the effect of somatic mosaicism on clinical outcomes can vary depending on contextual factors, such as the developmental origin of a variant or the number and type of cells affected. In this review, we highlight current knowledge regarding the role of somatic mosaicism in brain disorders and how biological context can mediate phenotypes. First, we identify the origins of brain somatic variation throughout the lifespan of an individual. Second, we explore recent discoveries that suggest somatic mosaicism contributes to various brain disorders. Finally, we discuss neuropathological associations of brain mosaicism in different biological contexts and potential clinical utility.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reflections on a Career in Pediatric Neuropathology, with a Note of Gratitude. 对儿科神经病理学职业生涯的思考，以及感恩之情。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-07-16 DOI: 10.1146/annurev-pathmechdis-111523-023355
Hannah C Kinney
{"title":"Reflections on a Career in Pediatric Neuropathology, with a Note of Gratitude.","authors":"Hannah C Kinney","doi":"10.1146/annurev-pathmechdis-111523-023355","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023355","url":null,"abstract":"<p><p>I am honored to be asked by the journal to write this personal essay about my career in pediatric neuropathology-a life of immense satisfaction, meaning, and fulfillment. My motivation to enter this discipline is highlighted, as is my decision to perform brain research in the sudden infant death syndrome, the leading cause of postneonatal infant mortality in the United States today. I also touch upon collaborations, mentoring, and experiences along the way-especially with the light microscope. I close with thoughts about the future of the discipline from my perspective as a lifelong devotee.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hypoxia-Induced Signaling in Gut and Liver Pathobiology. 缺氧诱导的肠道信号传导和肝脏病理生物学。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 Epub Date: 2023-10-13 DOI: 10.1146/annurev-pathmechdis-051122-094743
Sumeet Solanki, Yatrik M Shah
{"title":"Hypoxia-Induced Signaling in Gut and Liver Pathobiology.","authors":"Sumeet Solanki, Yatrik M Shah","doi":"10.1146/annurev-pathmechdis-051122-094743","DOIUrl":"10.1146/annurev-pathmechdis-051122-094743","url":null,"abstract":"<p><p>Oxygen (O<sub>2</sub>) is essential for cellular metabolism and biochemical reactions. When the demand for O<sub>2</sub> exceeds the supply, hypoxia occurs. Hypoxia-inducible factors (HIFs) are essential to activate adaptive and survival responses following hypoxic stress. In the gut (intestines) and liver, the presence of oxygen gradients or physiologic hypoxia is necessary to maintain normal homeostasis. While physiologic hypoxia is beneficial and aids in normal functions, pathological hypoxia is harmful as it exacerbates inflammatory responses and tissue dysfunction and is a hallmark of many cancers. In this review, we discuss the role of gut and liver hypoxia-induced signaling, primarily focusing on HIFs, in the physiology and pathobiology of gut and liver diseases. Additionally, we examine the function of HIFs in various cell types during gut and liver diseases, beyond intestinal epithelial and hepatocyte HIFs. This review highlights the importance of understanding hypoxia-induced signaling in the pathogenesis of gut and liver diseases and emphasizes the potential of HIFs as therapeutic targets.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"291-317"},"PeriodicalIF":36.2,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41219356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Within-Host Evolution of Bacterial Pathogens in Acute and Chronic Infection. 急性和慢性感染中细菌病原体的宿主内进化。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 Epub Date: 2023-10-13 DOI: 10.1146/annurev-pathmechdis-051122-111408
John P Dekker
{"title":"Within-Host Evolution of Bacterial Pathogens in Acute and Chronic Infection.","authors":"John P Dekker","doi":"10.1146/annurev-pathmechdis-051122-111408","DOIUrl":"10.1146/annurev-pathmechdis-051122-111408","url":null,"abstract":"<p><p>Bacterial pathogens undergo remarkable adaptive change in response to the selective forces they encounter during host colonization and infection. Studies performed over the past few decades have demonstrated that many general evolutionary processes can be discerned during the course of host adaptation, including genetic diversification of lineages, clonal succession events, convergent evolution, and balanced fitness trade-offs. In some cases, elevated mutation rates resulting from mismatch repair or proofreading deficiencies accelerate evolution, and active mobile genetic elements or phages may facilitate genome plasticity. The host immune response provides another critical component of the fitness landscapes guiding adaptation, and selection operating on pathogens at this level may lead to immune evasion and the establishment of chronic infection. This review summarizes recent advances in this field, with a special focus on different forms of bacterial genome plasticity in the context of infection, and considers clinical consequences of adaptive changes for the host.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"203-226"},"PeriodicalIF":36.2,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41219359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chance and Opportunity: A Personal Story. 机会与机遇：一个人的故事
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 DOI: 10.1146/annurev-pathmechdis-052323-040230
Abul K Abbas
{"title":"Chance and Opportunity: A Personal Story.","authors":"Abul K Abbas","doi":"10.1146/annurev-pathmechdis-052323-040230","DOIUrl":"10.1146/annurev-pathmechdis-052323-040230","url":null,"abstract":"<p><p>This article summarizes my personal life story, from early education in India to research, teaching, and other activities in Boston and San Francisco. I have tried to illustrate how unplanned events shape one's path, and why the willingness to go with the flow is among one's most valuable attributes.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"19 ","pages":"1-10"},"PeriodicalIF":36.2,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Control of Cell Death in Health and Disease. 控制健康和疾病中的细胞死亡。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 Epub Date: 2023-10-03 DOI: 10.1146/annurev-pathmechdis-051022-014433
Nobuhiko Kayagaki, Joshua D Webster, Kim Newton
{"title":"Control of Cell Death in Health and Disease.","authors":"Nobuhiko Kayagaki, Joshua D Webster, Kim Newton","doi":"10.1146/annurev-pathmechdis-051022-014433","DOIUrl":"10.1146/annurev-pathmechdis-051022-014433","url":null,"abstract":"<p><p>Apoptosis, necroptosis, and pyroptosis are genetically programmed cell death mechanisms that eliminate obsolete, damaged, infected, and self-reactive cells. Apoptosis fragments cells in a manner that limits immune cell activation, whereas the lytic death programs of necroptosis and pyroptosis release proinflammatory intracellular contents. Apoptosis fine-tunes tissue architecture during mammalian development, promotes tissue homeostasis, and is crucial for averting cancer and autoimmunity. All three cell death mechanisms are deployed to thwart the spread of pathogens. Disabling regulators of cell death signaling in mice has revealed how excessive cell death can fuel acute or chronic inflammation. Here we review strategies for modulating cell death in the context of disease. For example, BCL-2 inhibitor venetoclax, an inducer of apoptosis, is approved for the treatment of certain hematologic malignancies. By contrast, inhibition of RIPK1, NLRP3, GSDMD, or NINJ1 to limit proinflammatory cell death and/or the release of large proinflammatory molecules from dying cells may benefit patients with inflammatory diseases.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"157-180"},"PeriodicalIF":36.2,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41156198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clonal Hematopoiesis, Inflammation, and Hematologic Malignancy. 克隆性造血、炎症和血液系统恶性肿瘤。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 Epub Date: 2023-10-13 DOI: 10.1146/annurev-pathmechdis-051222-122724
Rashmi Kanagal-Shamanna, David B Beck, Katherine R Calvo
{"title":"Clonal Hematopoiesis, Inflammation, and Hematologic Malignancy.","authors":"Rashmi Kanagal-Shamanna, David B Beck, Katherine R Calvo","doi":"10.1146/annurev-pathmechdis-051222-122724","DOIUrl":"10.1146/annurev-pathmechdis-051222-122724","url":null,"abstract":"<p><p>Somatic or acquired mutations are postzygotic genetic variations that can occur within any tissue. These mutations accumulate during aging and have classically been linked to malignant processes. Tremendous advancements over the past years have led to a deeper understanding of the role of somatic mutations in benign and malignant age-related diseases. Here, we review the somatic mutations that accumulate in the blood and their connection to disease states, with a particular focus on inflammatory diseases and myelodysplastic syndrome. We include a definition of clonal hematopoiesis (CH) and an overview of the origins and implications of these mutations. In addition, we emphasize somatic disorders with overlapping inflammation and hematologic disease beyond CH, including paroxysmal nocturnal hemoglobinuria and aplastic anemia, focusing on VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Finally, we provide a practical view of the implications of somatic mutations in clinical hematology, pathology, and beyond.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"479-506"},"PeriodicalIF":36.2,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41219352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of the Microenvironment in Glioma Pathogenesis. 微环境在胶质瘤发病机制中的作用。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 Epub Date: 2023-10-13 DOI: 10.1146/annurev-pathmechdis-051122-110348
Maya Anjali Jayaram, Joanna J Phillips
{"title":"Role of the Microenvironment in Glioma Pathogenesis.","authors":"Maya Anjali Jayaram, Joanna J Phillips","doi":"10.1146/annurev-pathmechdis-051122-110348","DOIUrl":"10.1146/annurev-pathmechdis-051122-110348","url":null,"abstract":"<p><p>Gliomas are a diverse group of primary central nervous system tumors that affect both children and adults. Recent studies have revealed a dynamic cross talk that occurs between glioma cells and components of their microenvironment, including neurons, astrocytes, immune cells, and the extracellular matrix. This cross talk regulates fundamental aspects of glioma development and growth. In this review, we discuss recent discoveries about the impact of these interactions on gliomas and highlight how tumor cells actively remodel their microenvironment to promote disease. These studies provide a better understanding of the interactions in the microenvironment that are important in gliomas, offer insight into the cross talk that occurs, and identify potential therapeutic vulnerabilities that can be utilized to improve clinical outcomes.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"181-201"},"PeriodicalIF":36.2,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41219358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epigenomic Characterization of Lymphoid Neoplasms. 淋巴肿瘤的表观基因组特征。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 Epub Date: 2023-10-13 DOI: 10.1146/annurev-pathmechdis-051122-100856
Martí Duran-Ferrer, José Ignacio Martín-Subero
{"title":"Epigenomic Characterization of Lymphoid Neoplasms.","authors":"Martí Duran-Ferrer, José Ignacio Martín-Subero","doi":"10.1146/annurev-pathmechdis-051122-100856","DOIUrl":"10.1146/annurev-pathmechdis-051122-100856","url":null,"abstract":"<p><p>Lymphoid neoplasms represent a heterogeneous group of disease entities and subtypes with markedly different molecular and clinical features. Beyond genetic alterations, lymphoid tumors also show widespread epigenomic changes. These severely affect the levels and distribution of DNA methylation, histone modifications, chromatin accessibility, and three-dimensional genome interactions. DNA methylation stands out as a tracer of cell identity and memory, as B cell neoplasms show epigenetic imprints of their cellular origin and proliferative history, which can be quantified by an epigenetic mitotic clock. Chromatin-associated marks are informative to uncover altered regulatory regions and transcription factor networks contributing to the development of distinct lymphoid tumors. Tumor-intrinsic epigenetic and genetic aberrations cooperate and interact with microenvironmental cells to shape the transcriptome at different phases of lymphoma evolution, and intraclonal heterogeneity can now be characterized by single-cell profiling. Finally, epigenetics offers multiple clinical applications, including powerful diagnostic and prognostic biomarkers as well as therapeutic targets.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"371-396"},"PeriodicalIF":36.2,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41219354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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